Design of Peptide Molecules to Mimic the Metal Binding Sites of Proteins

Abstract

The molecular design to mimic the metal-binding site of a protein molecule entails abstracting the minimum requirements which must be retained in a molecule in order to maintain parameters controling the geometry, metal-binding ligands and microenvironment at the metal-binding site. A linear peptide may be designed to mimic a site which is located on a short linear amino acid sequence. However, when the metal-binding ligands originate from different parts of the polypeptide backbone, a cyclic peptide should be designed with amino acid residues having appropriate side chains. For the purpose of the design, building of suitable molecular models are essential. This can be supplemented by conformational calculations. Three examples are presented for the molecular design of the metal-binding sites: Copper(II)-transport site of human albumin, Zn(II)-binding sites of two metalloenzymes: carboxypeptidase and carbonic anhydrase.